The major objectives of this proposed project are to identify and characterize receptor and effector molecules on T cells. These experiments will combine in vitro functional tests, such as killing by cytotoxic T lymphocytes (CTL), antigen-specific T proliferation and in vitro antibody responses with immunochemical analyses to identify the relevant functional surface structures. Other experiments are proposed to determine whether specific cell surface markers are associated with subsets of rabbit T cells and to develop procedures for generating and detecting alloreactive rabbit CTL. T-helper cells and CTL appear to share idiotypes with circulating immunoglobulin (lg) of the same specificity. However, it has been exceedingly difficult to demonstrate unambiguously that the functional T-cell receptor is associated with an lg VH domain or that any lg determinants are T-cell associated. The rabbit is a particularly useful species for studies of this sort because it possesses a well-characterized set of allotypic lg markers, especially the a locus determinants which are located in the VH domain. The current project proposes to test whether antisera to lg determinants can inhibit or stimulate rabbit T cells involved in several functions, such as xenogeneic cell mediated cytolysis, T help in an antibody response or T-cell proliferation stimulate by antigens or lymphocytes. If allotypic or other lg markers can be shown to occur on these cells, then attempts will be made to isolate and characterize the molecule(s) expressing these determinants. The applicant has already found that anti-thymocyte serum (ATS) can interfere with cytolysis by rabbit CTL. Experiments are proposed to determine how the ATS inhibition occurs and to isolate the T-cell surface component(s) which are involved. The ATS may block CTL by binding to effector molecules and/or to some invariant region of the T-cell receptor. Other experiments are proposed to develop procedures for stimulating and detecting alloreactive rabbit CTL for use in future genetic analyses.